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AAddddrreessss ffoorr ccoorrrreessppoonnddeennccee:: Piotr Chomik DDS, Department of Oral and Maxillofacial Surgery, Medical University of Gdansk, 7 Smoluchowskiego St, 80-214 Gdansk, Poland, phone: +48 505 172 685, fax: +48 58 349 31 00, e-mail: piotr.chomik@gumed.edu.pl

Solitary fibrous tumor in the oral cavity: a case reportand diagnostic dilemma

Piotr Chomik1, Adam Michcik1, Igor Michajłowski2, Michał Sobjanek2, Adam Włodarkiewicz1,2

1Department of Oral and Maxillofacial Surgery, Medical University of Gdansk, PolandHead: Prof. Adam Włodarkiewicz MD, DDS, PhD2Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, PolandHead: Prof. Roman Nowicki MD, PhD

Postep Derm Alergol 2012; XXIX, 5: 395-400

DOI: 10.5114/pdia.2012.31495

Case report

AbstractThe investigators wish to discuss the diagnostic difficulties, histology and immunohistochemical profile of a soli-tary fibrous tumor (SFT) based on the presented case, as well as previously reported cases within the oral cavity.A young woman was referred to the Department of Maxillofacial Surgery, Medical University of Gdansk, Poland,due to a considerable palpable mass within the hard palate. Pain and discomfort caused by the tumor’s locationwere the main complaints. A clinical examination revealed a tumor of the right hard palate along the alveolar crest,measuring approximately 5 cm × 3 cm. Panoramic X-ray depicted a bone defect of the alveolar crest around tooth17. Histological and immunohistochemical evaluation of the biopsy specimen and resected tumor establishedthe diagnosis of SFT. This rare spindle cell neoplasm of mesenchymal origin is typical of serosal sites and approxi-mately 80 cases within the head and neck region have been reported so far. The hard palate is one of the least fre-quent locations. Approximately 5-20% of lesions may present features of aggressiveness. The authors wish to empha-size that the diagnosis of SFT is challenging due to a relatively small number of cases reported in the literature,uncertain etiology of the tumor, as well as clinical and histological similarity to other, more frequently occurringbenign neoplasms of mesenchymal origin, i.e. hemangiopericytoma, myofibroblastoma, schwannoma, neurofibro-ma, leiomyoma, as well as inflammatory disorders, especially nodular fasciitis. Radical excision of the tumor ismandatory for effective treatment due to the possibility of recurrence and malignant transformation after subrad-ical resection.

KKeeyy wwoorrddss:: solitary fibrous tumor, oral cavity, hard palate, diagnosis.

Introduction

A solitary fibrous tumor (SFT) is a spindle cell neoplasmof mesenchymal origin with a particular predilection forserosal sites [1-4]. Klemperer and Rabin described the firstcase in the visceral pleura in 1931 [5]. Convincingly, dueto such a location, it was initially stated that this wasa benign variant of mesothelioma [2, 6]. Subsequent ultra-structural research revised this opinion and revealed thatSFT originated from interstitial stem cells localized main-ly in the soft tissues of various body sites [2, 7]. Despiteknowledge of the tumor’s origin and reproducibleimmunohistochemical profile, its biology is still incom-pletely explained [2, 8].

Most cases express benign behavior, although accord-ing to the literature, about 5-20% of tumors may present

features of aggressiveness along with local recurrences,as well as distant metastases to the liver, lungs, bones,mesentery and the retroperitoneal space [7, 9, 10]. Recur-rences usually present more advanced histology than pri-mary tumors. On the other hand, some cases of SFT withhistological features of malignancy clinically present asbenign tumors, which unambiguously indicates thatthe biology of particular cases cannot be predicted exclu-sively based on the histological diagnosis [4].

Data in the literature show that SFT within the headand neck comprise only about 3% of cases, mostly affect-ing the oral cavity [1]. Tumors within the thyroid gland,larynx, epiglottis, parapharyngeal space, major salivaryglands, nasopharynx, paranasal sinuses, orbit, as well ascerebral meninges, are considerably rare [7]. Most patients

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with SFT of the oral cavity present with a slow growing,non-tender mass of various dimensions located withinthe submucosal tissue [1, 11, 12].

Regarding the morphology and clinical appearanceof SFT, the differential diagnosis should include tumorsof the salivary glands, lipoma, mucocoele, vessel malfor-mations, lymphoma, as well as odontogenic abscesses [9, 12, 13]. On the other hand, due to its histological fea-tures, SFT should be distinguished from hemangioperi-cytoma, myofibroblastoma, schwannoma, neurofibroma,leiomyoma and inflammatory diseases, such as nodularfasciitis [9, 10, 14-16].

Herein, the authors present a case of a young womandiagnosed with SFT of the hard palate after initial histo-logical and immunohistochemical analysis of a biopsyspecimen. Treatment methods, histological features andan immunohistochemical profile are discussed.

Case report

A 33-year-old woman was referred to the Departmentof Maxillofacial Surgery, Medical University of Gdansk,Poland, in order to diagnose and treat a tumor of the hardpalate. The lesion had appeared 1.5 years earlier and grew continually. On the day of admission, the patient complained of frequent pain and discomfort due tothe tumor’s location. The anamnesis revealed hypothy-roidism and the patient remained under regular endo -crinologic control.

Clinical examination revealed a tumor of the right hardpalate along the alveolar crest in close proximity to teeth15-17, measuring approximately 5 cm × 3 cm. The lesionpresented with a rather soft consistency, was non-tender

during palpation, and was covered with mucosa, whichtended to be slightly paler compared to the surroundingtissue (Figure 1). Panoramic X-ray revealed a bone defectof the alveolar crest around tooth 17 (Figure 2).

Microscopic evaluation of the biopsy specimen stat-ed: spindle cell neoplasm with slight nuclear pleomor-phism and the presence of vessels, part of which expressa sharpened (“staghorn”) shape. Phenotype: CD34+,S100+, SMA–, GFAP–, CK AE 1/3–, NF–, EMA–. Overall,the microscopic picture is most typical of a solitary fibroustumor.

Following such a diagnosis, the tumor was resectedalong with a 1 cm margin of clinically unsuspected tissueunder general anesthesia (Figures 3, 4). Pathologic eval-uation of the excised lesion confirmed the initial diagno-sis: solitary fibrous tumor; phenotype: CD34+, SMA–,S100–, CD99+, bcl2+, CK AE 1/3–. The patient remainsunder regular clinical follow-up, currently without signsof recurrence.

Discussion

Solitary fibrous tumor typically occurs betweenthe fourth and eighth decade of life with equal fre quencyin both sexes [11, 12, 15]. The etiopathogenesis of thetumor remains unclear. Two theories have been advocat-ed in the literature to clarify this issue [7]. The first oneassumes multidirectional differentiation of fibroblasts andmesenchymal multipotential cells in connective tissue [7].The second one relates to the existence of specializedcells, capable of differentiation towards mesothelium [7].Nevertheless, most evidence advocates the theoryof the mesenchymal origin of SFT [7, 17].

Moreover, lesions appearing in the oral cavity have notbeen accompanied by systemic symptoms in any of thereported cases. On the other hand, these symptoms aretypical of SFT at serosal sites, such as the pleura [4, 15].

Among approximately 80 cases of SFT in the oral cav-ity, the most frequent sites were the tongue and buccaltissues, which may indicate irritation as a potential etio-logic factor for this tumor arising in these particular loca-tions [1, 15].

Piotr Chomik, Adam Michcik, Igor Michajłowski, Michał Sobjanek, Adam Włodarkiewicz

FFiigguurree 11.. Tumor of the right hard palate along the alveolarcrest in close proximity to teeth 15-17 (arrowhead). The cove-ring mucosa tends to be slightly paler compared to the sur-rounding tissues

FFiigguurree 22.. Panoramic X-ray of the patient revealed a bonedefect of the alveolar crest around tooth 17 (arrowhead)

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Solitary fibrous tumor in the oral cavity: a case report and diagnostic dilemma

FFiigguurree 33.. Intraoperative view directly after tumor resection.The bone defect is visible within the tumor site FFiigguurree 44.. The tumor mass directly after resection

Concerning the similarity to other more frequentlyoccurring neoplasms of mesenchymal origin, both histo-logical and immunohistochemical diagnosis may be chal-lenging even to the experienced pathologist. Becauseof this, Chan et al. [18] established diagnostic criteriawhich enable establishing a diagnosis of SFT. They includeclinical, histological and immunohistochemical charac-teristics of the tumor, among others clinically fair demar-cation of the lesion from surrounding tissues, alternatinghypercellular foci and hypocellular sclerotic foci, bland-looking, short and spindly or ovoid cells with scanty andpoorly defined cytoplasm, few mitotic figures (< 4/10 HPF),haphazard, storiform or fascicular arrangement of spindlycells (a so-called “patternless pattern”), intimate inter-twining of thin or thick collagen fibrils with spindly cells,and immunohistochemical positivity for CD34, which isobligatory to confirm the diagnosis of extrapleural SFT[15, 16, 19].

Additionally, the lack of encapsulation of the tumor,as well as small cell dimensions and cell membrane dis-turbances may be observed. The cytoplasm presentsa weak eosinophilic reaction and spindly nuclei containdiffuse chromatin and small nucleoli [7, 15, 16]. Fairlynumerous blood vessels presenting a typical “staghornpattern” are common, which is particularly seen amongother features mentioned above in the microscopic spec-imen of the presented case (Figure 5), as well as more orless abundant infiltrates of mast cells.

As mentioned above, histology of SFT is typical of mostneoplasms of mesenchymal origin, thus immunohisto-chemical labeling is obligatory for a correct diagnosis.The vast majority of SFTs express a positive reaction forCD34 (Figure 6) and vimentin [7, 9]. The same reactionmay be observed for CD99 and bcl-2, although this is notthe rule [9]. At times, positive staining for factor XIIIa maybe present [20]. A negative reaction is common for S-100protein (Figure 7), cytokeratin (Figure 8), desmin and

actin [12]. In the presented case, immunohistochemicalevaluation of the biopsy specimen demonstrated posi-tive staining for S-100 protein; nevertheless, the resect-ed tumor presented an unequivocally negative reaction.Eventually, it was stated that the biopsy specimen exam-ination revealed a false positive result for S-100 protein.This molecule is common in nerve sheaths, thus positivestaining is typical of lesions of neuronal origin, for exam-ple schwannoma or neurofibroma.

Five to twenty percent of SFT cases have been shownto display both microscopic and clinical characteristicsof malignancy [1, 4, 7]. Histologically, these tumors tendto contain greater amounts of cells with focally observedsignificant alterations, features of necrosis, numerousmitotic figures, as well as infiltrated borders [7]. Differ-entiation between benign and malignant variants onthe microscopic level is primarily based on the presence

FFiigguurree 55.. With hematoxylin and eosin staining, haphazar-dly arranged spindly cells are visible (arrowhead). Bundlesof collagen fibers and fairly numerous blood vessels pre-senting the typical “staghorn pattern” (arrow) are also seen.Magnification 100×

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Piotr Chomik, Adam Michcik, Igor Michajłowski, Michał Sobjanek, Adam Włodarkiewicz

and number of mitotic figures which are sparse or evenabsent in benign cases, as well as nuclear alterations typ-ical of malignant cases [7]. Fusconi et al. [6] have alsodescribed the presence of sarcoma-like foci within SFT aswell as the development of sarcoma at the location of pre-viously resected SFT as a malignancy criterion of the lat-ter. Features of clinical malignancy include first of all localrecurrences, which may occur even a few years after totalresection of the primary tumor, distant metastases, par-ticularly to the liver, lungs, bones and mesentery, as wellas the retroperitoneal space [9]. Especially important isthe fact that recurrences usually present a more advancedphenotype compared to primary lesions.

Total surgical resection along with macroscopicallyunsuspected tissue margins is the treatment of choice inSFT cases [1, 4, 7, 9]. Reports of postoperative radiother-apy and chemotherapy with adriamycin and dacarbazinein cases of large tumors with positive margins are avail-able in the literature [7, 9]. In the reported case, total sur-gical resection, which was confirmed by histologicalexamination of the excised tissue specimen, was con-sidered to be sufficient treatment.

Differential diagnosis of SFT relates to other mes-enchymal tumors, including hemangiopericytoma, myofi-broblastoma, schwannoma, neurofibroma, leiomyoma,as well as inflammatory disorders such as nodular fasci-itis [9, 10, 12, 14-16]. The most challenging issue is the dif-ferentiation between SFT and hemangiopericytoma dueto very similar histological and immunohistochemical pro-files. It is believed that hemangiopericytoma is morehomogenous. It also contains fewer collagen fibers andmore cells compared to SFT [12]. Positive CD34 stainingtends to be more focal and less regular in cases of heman-giopericytoma [12].

Myofibroblastoma histologically presents uniformspindly cells arranged in short bundles. Moreover, mole-cular evaluations have revealed that these cells differen-tiate into both fibroblasts and smooth muscle cells, whichresults in positive immunohistochemical staining towardssmooth muscle actin (SMA). As mentioned above, sucha reaction is negative in cases of SFT [10].

Spindle cell neoplasms of neuronal origin, includingschwannoma and neurofibroma, display some clinicaland immunohistochemical attributes similar to SFT. Theselesions are typically fairly well circumscribed from sur-rounding tissues, which they owe to the presenceof a capsule around the tumor. On the other hand, despiteits fair demarcation from surrounding tissues, SFT is anunencapsulated tumor [10]. Distinct positive staining forS-100 protein, which is typical of nerve sheaths, is a gen-eral immunohistochemical hallmark of neuronal tumors.As mentioned above, SFT displays a negative reaction forS-100 protein, which disqualifies its neuronal origin [14].

Leiomyoma is characterized by more fascicular andregular arrangements of spindly cells compared to SFT [10]. Ultrastructural findings present the differentia-

FFiigguurree 66.. Immunopositive CD34 reaction expressed by tumorcells (arrowhead) and negative reaction within vessel walls(arrow). Magnification 100×

FFiigguurree 77.. SFT cells are typically immunonegative for S-100protein (arrowhead), which is specific of nerve sheaths.Magnification 100×

FFiigguurree 88.. SFT cells demonstrate negative immunohistoche-mical reactions for CKAE 1 and CKAE 3 (arrowheads). Magni-fication 100×

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Solitary fibrous tumor in the oral cavity: a case report and diagnostic dilemma

tion of these cells towards smooth muscle, thus immuno-histochemical staining for SMA is positive. Additionally,immunoreactions towards CD34 and bcl-2 are negativein cases of leiomyoma [10]. In conclusion, differentiationbetween SFT and leiomyoma on an immunohistochemi-cal level should not be a challenge.

Nodular fasciitis (NF) is a separate inflammatory enti-ty which should be taken into consideration in the dif-ferential diagnosis of SFT. Clinically, both disorders rep-resent fair circumscription from surrounding tissues.Moreover, spindly cells are common for both lesionsmicroscopically. On the other hand, in cases of SFT,the presence of mature bundles of collagen fibers can befound, which are absent in NF. Moreover, a large numberof relatively loosely and regularly arranged cells is typicalof NF [21]. Immunohistochemical evaluation revealsthe most evident differences between these two entities.In cases of NF, cells stain positive for SMA, whereas pos-itive immunostaining for CD34 is visible only in close prox-imity to vessel walls. On the other hand, SFT stains unam-biguously negative for SMA, whereas staining for CD34is intensively positive within the entire lesion [21].

In order to examine the pathology of SFT entirely,Manor and Bodner [22] analyzed chromosomal aberra-tions within their case and summarized similar analysesof other researchers. So far, it has been proven that chro-mosomal aberrations typical of SFT may be characterizedby additional chromosomes 2, 7, 8, 9, 10, 18 and 21 intumor cells, additional arms of chromosomes 12p, 12qand 15q, loss of arms 4q, 5p, 6, 9p, 13q, 15q, and 20p, lossof entire chromosomes 6, 10, 17, 21, 22 and X [23], as wellas complex translocations within chromosomes 1, 17 and18 [22]. It has been also stated that the most frequentchromosomal aberration in SFT is the loss of arm 13q [22].The significance of this abnormality and its influence onthe development and biology of the tumor has not beenestablished yet.

Ultrastructural analysis of SFT performed by Ide et al.[20] suggested that it may be responsible for intensiveangiogenesis at a particular stage of its development,which results in the typical “staghorn pattern” of vesselarrangement in the microscopic evaluation of SFT.

In summary, we state that in spite of the fairly well-known histological and immunohistochemical profileof SFT, its etiopathogenesis is still insufficiently explained.Consequently, the clinical behavior of the tumor and itsbiology are extraordinarily difficult to predict, and localrecurrences as well as distant metastases are possibleeven a few years after histologically proven radical resec-tion. With an awareness of these facts, patients mustremain under long-term follow-up after the treatmenthas been completed. Further molecular studies in orderto accurately explore the biology of SFT and applicationof the most effective treatment at an early stage are cru-cial priorities.

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